Besides the administration of antibodies or tyrosine kinase inhibitors for malignancies, the typical treatment for many cancers is the administration of radiation therapy and chemotherapeutic agents. However, side effects are a limiting factor in radiation treatments. Combination chemotherapy has some success in reaching partial or complete responses. Unfortunately, the remissions obtained through chemotherapy are often not durable.
Congenital hyperinsulinism (CHI, OMIM 256450) is a genetic disorder of pancreatic β-cell function characterized by failure to suppress insulin secretion in the presence of hypoglycemia, resulting in brain damage or death if inadequately treated.
Neuroendocrine tumors including such cancers as insulinoma, hepatomas, mesotheliaoma and fibrosarcoma may also cause hyperinsulinemia accompanied by hypoglycemia.
Gangliosides are sialic acid containing glycosphingolipids. Gangliosides are normal components of plasma membranes which are particularly abundant in the nervous system. In humans, gangliosides are most abundant in the gray matter of the brain, particularly in nerve endings. As a result, the addition of one or more glycolipids for cancer (e.g., during immunotherapy, such as antibodies or tyrosine kinase inhibitors), patients suffering from hyperinsulinemia, hypoglycemia or hypersinsulinemia with hypoglycemia or neurological disorders (e.g., Huntington's Disease, multiple systems atrophy, atypical Parkinson's disease, tauopathies) may reduce the mortality and/or morbidities associated with each disease. Attempts have been made to use gangliosides in the treatment of disorders of the nervous system. This has led to the development of synthetic gangliosides as well as natural ganglioside containing compositions for use in the treatment of disorders of the nervous system (see, U.S. Pat. Nos. 4,476,119; 4,593,091; 4,639,437; 4,707,469; 4,713,374; 4,716,223; 4,849,413; 4,940,694; 5,045,532; 5,135,921; 5,183,807; 5,190,925; 5,210,185; 5,218,094; 5,229,373; 5,260,464; 5,264,424; 5,350,841; 5,424,294; 5,484,775; 5,519,007; 5,521,164; 5,523,294; 5,677,285; 5,792,858; 5,795,869; and 5,849,717).
There exists a need in the art for ganglioside compounds and methods of treatment which use the compounds to treat diseases such as cancer, hyperinsulinemia, atypical Parkinson's disease, multiple systems atrophy, Huntington's disease, tauopathies or ganglioside deficient states or disorders, including neurological conditions. Ideally, such compounds act in a manner similar to, or better than, the natural gangliosides for the prophylaxis, treatment and cure of such states or disorders.